dm+d

Unassigned

New Medicines

Critical limb ischaemia in patients with diabetes mellitus unsuitable for endovascular or surgical revascularisation

Information

New molecular entity
Ixaca
Ixaca

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
None
Jun 22Ixaka and Minaris Regenerative Medicine sign an agreement to enable technology transfer as well as clinical and commercial manufacture of REX-001. Under the terms of agreement, Minaris will perform technology transfer of REX-001 manufacturing and QC testing activities from Ixaka ’s Seville facilities to Minaris’ facilities near Munich. The move will take place in preparation for the upcoming REX-001-006 PIII trial. The scope of the manufacturing agreement includes the scale-up and technology transfer with the goal of supplying the PIII trials and supporting commercial supplies in the EU and later in the US [14].
Jan 21Ixaca (formerly Rexgenero) has launched with additional financing from existing shareholders totalling over £40m. Its lead product is REX-001 (rexmyelocel-T). Its focus is now on accelerating progress to help realise the potential for durable and curative cell and gene therapies [10].
Oct 20Rexgenero announces that the Independent Data Monitoring Committee (IDMC) for its REX-001 PIII clinical trial recently met to review patient safety and tolerability data from the initial 22 subjects. Based on this review, the IDMC unanimously agreed to continue the trial unchanged due to no significant safety concerns. An interim analysis of the ongoing PIII trial is planned for Q2 22; results for the primary endpoint are expected in the Q2 23 [9].
Apr 20Rexgenero is seeking development and marketing partners to take these products to the market globally [7].
Mar 17Will be filed in the EU via the centralised procedure [2].
Apr 16MHRA issues a Promising Innovative Medicine Designation (PIM) for rexmyelocel T, a first step to early access to medicines scheme (EAMS) for rexmyelocel T for treatment of critical limb ischaemia based on PII data. The company intends to file for a scientific opinion (step 2) under the EAMS by the end of 2016 [3].
Jun 15Classified as an ATMP (tissue engineered product) by the EMA [1].

Category

Autologous stem cell therapy made of bone marrow-derived mononuclear cells (BM-MNCs) taken from the patient's own bone marrow and enriched for white blood cells. BM-MNCs are a rich source of progenitor cells, which directly contribute to vasculogenesis and indirectly stimulate angiogenesis through a paracrine mediated mechanism. Administered as a single dose through an intra-arterial catheter into the diseased vessels of the affected limb.
The estimated number of patients with peripheral arterial disease in the UK is 2.9 million. Of these, 20% suffer with CLI (145,582). In a large German study, it was found that 36% of the CLI population have DM. In the UK this would equate to over 31,078 CLI patients (Rutherford categories 4 and 5) with DM. It has been estimated that the proportion of patients with DM and CLI unsuitable for endovascular or surgical revascularization is between 50% and 90% of the population [2].
Critical limb ischaemia in patients with diabetes mellitus unsuitable for endovascular or surgical revascularisation
Intraarterial
Parenteral

Trial or other data

Oct 22PIII SALAMANDER trial (NCT03111238/REX-001-004) was stopped due to inactivity in Mar 21. Ixaca is planning a new REX-001-006 PIII trial, which will be the second of two PIII studies for REX-001 [14,15].
Sep 22PIII SALAMANDER trial (NCT03174522/REX-001-005) is now due to complete collection of primary outcome data in Dec 22 [15].
Sep 21Ixaka announce data from interim analysis is consistent with the effect observed in previous clinical trials, where REX-001 resulted in complete ulcer healing in >70% of patients. A second interim analysis is planned for when 12-month data is available for half of the participants. Primary completion is due by end of April 22 [13].
Jan 21No updates have been posted to the US trial registry for the two SALAMANDER trials (NCT03111238/REX-001-004 and NCT03174522/REX-001-005) so latest planned completion dates are not know. However, in Oct 20, the Independent Data Monitoring Committee (IDMC) after reviewing the patient safety and tolerability data from the initial 22 patients, unanimously recommended the continuation of the REX-001-005 trial [11,12].
Apr 20Rexmyelocel-L has been prioritised for potential TA guidance production. Topic has been passed to scoping team to prepare for a consultation exercise [16].
Apr 20The two pivotal adaptive PIII trials in patients with CLI and DM have had their design endorsed by the EMA including the two primary endpoints: the PIII study in patients with Rutherford stage 5 CLI is assessing the efficacy and safety with a primary endpoint of complete ulcer healing; the PIII study in patients with Rutherford stage 4 CLI is assessing the efficacy and safety of REX-001 with a primary endpoint of complete relief of ischaemic rest pain [7].
Jan 20UK trial sites for PIII studies - Cambridge, Cardiff, Newcastle [6]
Aug 18Both PIII trials (NCT03111238 and NCT03174522 ) are ongoing, with an estimated primary completion date of Oct 19 and Oct 20, respectively. [5]
Mar 17PIII (EudraCT2016-000240-34) study is currently recruiting patients in Austria and Spain [4].
Jul 16A PII trial of rexmyelocel T on therapeutic angiogenesis in 60 patients with diabetes, with non-vascularisable critical limb ischaemia has completed. Following treatment with rexmyelocel T, a majority of patients experienced a significant improvement in their clinical condition (as assessed by change in Rutherford category) with partial or complete ulcer healing and alleviation of rest pain. In angiographic imaging, majority of treated patients demonstrated improvement in blood vessels in the limb that might be responsible for the therapeutic efficacy of rexmyelocel T [3].
Jul 16Rexgenero initiates a PIII trial to evaluate the efficacy and safety of intra-arterial administration of rexmyelocel T for the treatment of patients with peripheral ischaemia, who also suffer from diabetes mellitus (REX-001-004). Clinically relevant response in the Rutherford category at 12 months after administration of Rexmyelocel-T or placebo. The randomised, double-blind, placebo-controlled trial would enrol 141 adult and elderly patients in Spain. The MHRA has confirmed that the proposed randomised, placebo-controlled design as well as the dose is acceptable [3].

Evidence based evaluations